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Biomedical subjects

T Mathiesen

Publications and source records attributed to T Mathiesen.

33 records · Page 2Linked to original sources
PubMed1989

Prolonged survival and vascularization of xenografted human glioblastoma cells in the central nervous system of cyclosporine A treated rats.

Glioblastoma cells from three established lines were transplanted in oculo and in cerebrum to rat hosts. A very low dose of Cyclosporine A was found sufficient to allow graft survival whereas grafts in non-immunosuppressed animals did not survive. Moderate immunosuppression permitted long term graft survival without aggressive growth of glioblastoma cells, creating a protracted course during which neither cell rejection nor tumor proliferation occurred. A tumor reminiscent of a glioblastoma was only seen in one animal on high immunosuppression. Phenotypic changes such as the induction of glial fibrillary acidic protein (GFAP) production and an astrocytic morphology were observed in the cells growing in oculo but not in cerebrum. Vascularization was easily demonstrated with laminin immunofluorescence but the endothelial proliferation typical of glioblastomas was not seen.

Animals↗
PubMed1989

Detection of antibodies against myelin basic protein and increased levels of HIV-IgG antibodies and HIV antigen after solubilization of immune complexes in sera and CSF of HIV infected patients.

Fifteen HIV seropositive patients were studied. It was possible to enhance detection of HIV antigen and HIV and myelin basic protein (MBP) antibodies after dissociation of immune complexes by acid hydrolysis. HIV p24 antigen was then detected in four patients, three of whom were previously antigen negative. In 14 patients the treatment resulted in increased anti-HIV IgG subclass levels. Anti-MBP IgG was detected in 12 patients. Intrathecal synthesis of anti-MBP IgG subclasses was found in eight patients, five of whom had symptoms from the central nervous system.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Antiviral IgM and IgG subclasses in varicella zoster associated neurological syndromes.

The varicella zoster virus (VZV) and herpes simplex virus (HSV) IgGl-4 subclasses were compared in serum and cerebrospinal fluid (CSF) of 22 patients with VZV-associated neurological symptoms, 12 patients with HSV-associated neurological symptoms and 14 controls. The clinical syndromes of the VZV-associated diseases comprised meningo-encephalitis, myelitis, myelopathies and polyneuropathies, mostly with a favourable outcome. A characteristic finding was an intrathecal synthesis of VZV IgG1 and HSV-3. Commonly also IgG2 and 4 were seen in CSF of VZV patients. Their intrathecally synthesised HSV IgG was restricted to IgG1. VZV IgG3 occurred in serum and/or CFS together with VZV IgM in 14 cases and may be a marker of recent VZV replication. In patients with HSV-associated neurological disease, a multi-IgG subclass HSV response and concomitant VZV antibodies restricted to IgG1 was found. Intrathecal synthesis of both HSV and VZV IgG occurred in 20 patients. Detection of two or more VZV or HSV specific IgG subclasses synthesised intrathecally identified the aetiological agent in 19 of these 20 cases.

Adult↗
PubMed1989

DNA-determination in the clinical management of patients with meningioma or haemangioblastoma.

The histopathology and clinical course of 15 benign (grade I) and nine anaplastic (grade II-III) meningiomas was reviewed and compared with the nuclear DNA distribution patterns of the tumour cells as determined by Feulgen staining with ensuing image and flow cytometry. In addition, eight haemangioblastomas were studied. One benign meningioma, three anaplastic meningiomas and two haemangioblastomas were aneuploid. The outcome could be well predicted from standard histopathological criteria and a critical evaluation of the extent of removal at operation. The determination of nuclear DNA contents did not add further information useful in the management of these meningioma patients. Histopathologically aggressive or frankly anaplastic tumours had a bad outcome. The clinical results underline the importance of aggressive treatment of anaplastic meningiomas.

Adult↗
PubMed1989

Analysis of a subclass-restricted HIV-1 gp41 epitope by omission peptides.

To define the amino acids involved in IgG subclass reactivity to two overlapping HIV-1 gp41 (E34/32; amino acid positions 582-613) peptides, sera from 18 HIV-infected individuals were studied. Peptides mimicking E34 but with single amino acid deletions or glycine substitutions were used to define the amino acid residues necessary for antibody binding. Two dominating immunogenic epitopes, containing highly hydrophilic amino acids, were found on the original peptide. Further analysis was undertaken with two corresponding omission sets of dodecapeptides representing halves of the complete E34 plus a terminal cystein peptide. The subclass reactivities usually differed between the patients with regard to the epitopes with which the different IgG subclasses reacted and also to the importance of different amino acids in antibody binding. The 600 glycine and the 601 lysine were involved in the binding of all IgG1, 2 and 4 and most IgG3. The development of E34/32-reactive IgM and IgG subclasses showed different patterns in four patients with primary HIV infections, contradicting the existence of a general pattern for the development of IgG subclasses to this peptide. The findings suggest that different progenitor clones are selected for synthesis of the different subclasses.

Amino Acid Sequence↗
PubMed1989

Mapping of IgG subclass and T-cell epitopes on HIV proteins by synthetic peptides.

Fifteen amino acid peptides, sequentially overlapping by 10 amino acids, were synthesized on the basis of the HTLV-III sequences of the gag and env proteins. They were used as antigens in IgG subclass ELISAs and T-cell stimulation assays. Sera and cells were obtained from 30 asymptomatic, HIV-infected homosexuals. In all subclasses reactivity was found to parts of the gag protein, while IgG1 dominated anti-env peptide responses. It was possible to delineate peptides showing restricted IgG subclass responses that were dominated by either IgG1, 2, 3 or 4. A negative correlation was generally observed between B-cell and T-cell reactivity, but a T-cell and B-cell co-operation was suggested by the response to two IgG1-restricted peptides. The IgG3-dominated epitopes were present in peptides previously known to be amphipathic and capable of T-cell stimulation. The analysis of subclass-restricted responses on the peptide level will assist the understanding of the subclass expression in vivo, since the peptide mapping approximates the delineation of a subclass-restricted response at the level of single epitopes.

Epitopes↗
PubMed1989

HIV-1 peptides induce a proliferative response in lymphocytes from infected persons.

In a comprehensive search for T-cell epitopes of HIV-1, several new regions were discovered. The analysis was performed with lymphocytes of HIV-1-infected persons in various stages of the infection. Peptides covering the entire group antigen (gag), and transmembrane (gp41) regions, and one-half of envelope (gp120) regions of HTLV-IIIB were studied. Both common and patient-unique responses were identified. Twelve common gag T-cell sites were discovered, as well as patient-unique activating peptides. The gag peptides elicited the most frequent cell responses and the responses remained in late stages of disease. Only 1 of the 12 T-cell activating gag peptides was reactive with specific anti-HIV IgG. Eighteen common env-representing peptides evoked T-cell responses. They could be grouped into four previously undescribed regions of gp120 and two known sites, the hypervariable stretch and part of the CD4 binding region. Cell responses to env peptides were common in early stages of disease and tended to decrease in ARC and AIDS. The gp41-representing peptides evoked a cellular response to a region close to the N-terminus of the hydrophobic transmembrane region. In addition to the T-cell activating peptides, peptides representing p15 and p19 as well as previously recognized regions of gp120 and gp41 appeared to be potent B-cell epitopes.

AIDS-Related Complex↗
PubMed1988

IgG subclass reactivity against human immunodeficiency virus (HIV) and cytomegalovirus in cerebrospinal fluid and serum from HIV-infected patients.

Cerebrospinal fluid (CSF) and serum samples from 17 patients seropositive for the human immunodeficiency virus (HIV) were analysed for specific IgG1-4 against HIV and cytomegalovirus (CMV). Measles IgG was studied as a reference to detect blood-brain barrier (BBB) defects. All patients had IgG1 antibodies against HIV in both CSF and serum, and all had CMV IgG1 in serum (16 in CSF). Anti-HIV IgG was synthesised intrathecally in 11 patients, IgG3 in three patients, and IgG4 in three patients. Intrathecal production of anti-CMV IgG1 was found in three patients, IgG2 in one, IgG3 in three, and IgG4 in one. Intrathecal anti-HIV IgG synthesis could be demonstrated in all stages of the disease. Analysis of all IgG subclasses allowed intrathecal HIV and/or IgG production to be detected also in patients in whom intrathecally synthesised IgG was restricted to IgG2, 3, or 4. The expression of HIV-specific IgG subclasses in CSF and serum was more restricted in AIDS patients than in HIV-infected persons without clinical AIDS. On the contrary, the largest number of CMV-specific IgG subclasses was found in AIDS patients. Intrathecal HIV or CMV IgG subclass production was seen both with and without neurological symptoms. The peripheral T4 cell counts were not obviously related to neurological symptoms. Even patients with low peripheral T4 cell counts had evidence of intrathecal antibody synthesis against HIV and sometimes CMV, suggesting a retained helper function of T cells in the central nervous system.

AIDS-Related Complex↗
PubMed1988

Specific IgG subclass reactivity in herpes simplex encephalitis.

Serum and cerebrospinal fluid (CSF) samples from 19 patients with a previous diagnosis of herpes simplex virus encephalitis (HSVE), from 14 patients with a previous diagnosis of non HSVE encephalitis and from 21 healthy subjects were examined to detect IgG subclasses 1-4 reactive with herpes simplex virus (HSV), cytomegalovirus (CMV) and varicella zoster virus (VZV). Antibodies to HSV were detected in CSF and serum from the 14 HSVE-patients with a reactivated HSV infection and from 3 of the 5 patients with a primary HSV infection. The predominant subclass pattern was an early HSV-specific IgG1 rise, followed by IgG3 and, more seldom, IgG4; HSV IgG2 was rarely seen. In HSVE patients, HSV IgG3 was absent in early samples and usually appeared 10-20 days after onset of disease. In 14 out of 16 seropositive healthy controls, on the other hand, HSV IgG3 was present in the CSF. Rising VZV IgG levels in serum and CSF were found in 11 HSVE patients. Eight of them showed signs of intrathecal VZV IgG1 synthesis. The VZV IgG reactivity was restricted to IgG1 in 7 of these whereas the HSV IgG subclass response also included IgG3 or 4. The appearance of several HSV IgG subclasses appeared to serve as a marker of HSV infection in spite of the serological VZV reaction, usually restricted to VZV IgG1. Intrathecal synthesis of the quantitatively minor HSV IgG3 and 4 subclasses was detected earlier than intrathecal synthesis of total HSV IgG, dominated by IgG1 in 4 patients with HSVE.

Encephalitis↗
PubMed1988

Acid hydrolysis of serum samples to increase detection of HIV antigen.

Sera from 32 HIV-infected patients and 20 controls were assayed for HIV antigen (HIV-Ag) and antibodies following acid hydrolysis. Acid hydrolysis, followed by neutralization immediately prior to the assay, was found to be a simple means to solubilize immune complexes and allowed recovery of 40-50% of complexed antigen. Following acid hydrolysis, HIV-Ag levels rose or became detectable in 22/32 patients and HIV IgG1-4 levels rose in 17/20 patients studied. The results show that complexed HIV-Ag may evade detection in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Combination ELISAs for antiviral antibodies in CSF and serum in patients with neurological symptoms and in healthy controls.

A combination enzyme-linked immunosorbent assay (ELISA) was designed to improve the estimation of serum: cerebrospinal fluid (CSF) antiviral IgG ratios. Microplate wells were coated with five different virus antigens. Serum and CSF from 66 patients referred for CSF serology and from 21 healthy controls were studied. In a comparison with serum: CSF IgG titre ratios, absorbance ratios were found to be suitable for the evaluation of intrathecal antiviral IgG synthesis. A slight blood-brain barrier (BBB) disturbance affected only the passage of albumin over the BBB, whereas a more pronounced BBB defect resulted in increased IgG levels in the CSF. Intrathecal antiviral IgG synthesis was demonstrated in 15 patients with viral CNS infections or inflammatory diseases. Very high serum: CSF antiviral IgG titre ratios and absorbance ratios, found in six patients, were interpreted as signs of diminished IgG passage over the BBB due to impaired CSF circulation.

Adult↗
PubMed1988

Neutralization capacity and antibody dependent cell-mediated cytotoxicity of separated IgG subclasses 1, 3 and 4 against herpes simplex virus.

IgG subclasses 1, 3 and 4 in sera from herpes simplex virus type 1 (HSV-1) seropositive donors were separated and their functions assayed. The main neutralizing activity to HSV-1 was found in the IgG1 fractions. Both IgG3 and IgG4 possessed higher neutralizing titres than IgG1 in relation to the respective HSV IgG subclass enzyme-linked immunosorbent assay (ELISA) titre. Addition of complement resulted in a strong enhancement of IgG3 neutralizing activity. HSV neutralizations by IgG1 and, surprisingly, IgG4 were also somewhat enhanced by complement. With the addition of complement, the contribution to neutralizing activity of IgG3 was calculated to increase from 31 to 40% of total IgG in HSV neutralization in native sera. The avidities of the IgG fractions to HSV glycoprotein C (gC) were estimated in a few sera but could not be correlated to neutralization results. Antibody dependent cell-mediated cytotoxicity (ADCC) was detectable mainly in IgG1 and 3 fractions of sera with high anti-HSV antibody titres.

Antibody Affinity↗
PubMedDate not supplied

A prognostic algorithm for assessment of subcapital femoral neck fractures.

A new method for prognostication of non-union in subcapital femoral neck fractures is presented. From routine pre- and post-operative films from 112 patients with Garden stage 2, 3, and 4 fractures 4 parameters were obtained: Cranial displacement, orientation of the nail in the femoral head, depth of nail inserted, and attainment of perfect reduction. These 4 variables were combined into a simple algorithm capable of non-union prediction at various levels of certainty (74-100%).

Adult↗